Stretch-induced increase in cardiac contractility is independent of myocyte Ca2+ while block of stretch channels by streptomycin improves contractility after ischemic stunning.

Stretching the cardiac left ventricle (LV) enhances contractility but its effect on myoplasmic [Ca(2+)] is controversial. We measured LV pressure (LVP) and [Ca(2+)] as a function of intra-LV stretch in guinea pig intact hearts before and after 15 min global stunning ± perfusion with streptomycin (STM), a stretch-activated channel blocker. LV wall [Ca(2+)] was measured by indo-1 fluorescence and LVP by a saline-filled latex balloon inflated in 50 μL steps to stretch the LV. We implemented a mathematical model to interpret cross-bridge dynamics and myofilament Ca(2+) responsiveness from the instantaneous relationship between [Ca(2+)] and LVP ± stretching. We found that: (1) stretch enhanced LVP but not [Ca(2+)] before and after stunning in either control (CON) and STM groups, (2) after stunning [Ca(2+)] increased in both groups although higher in STM versus CON (56% vs. 39%), (3) STM-enhanced LVP after stunning compared to CON (98% vs. 76% of prestunning values), and (4) stretch-induced effects on LVP were independent of [Ca(2+)] before or after stunning in both groups. Mathematical modeling suggested: (1) cooperativity in cross-bridge kinetics and myofilament Ca(2+) handling is reduced after stunning in the unstretched heart, (2) stunning results in depressed myofilament Ca(2+) sensitivity in the presence of attached cross-bridges regardless of stretch, and (3) the initial mechanism responsible for increased contractility during stretch may be enhanced formation of cross-bridges. Thus stretch-induced enhancement of contractility is not due to increased [Ca(2+)], whereas enhanced contractility after stunning in STM versus CON hearts results from improved Ca(2+) handling and/or enhanced actinomyosin cross-bridge cycling.